The invention relates to a flow system/bioreactor that can be used for testing medical devices, such as heart valve prostheses, and/or producing medical devices. The flow system may be useful for maintaining viable cells and/or culturing cells. In particular, the invention relates to systems with a flow, preferably pulsed flow, of a fluid.
To design and/or produce medical devices that contact a patient's body fluids and/or tissues, it may be desirable to use a system that can simulate physiological conditions. The desired features of a particular testing or production system generally depend on the particular objectives. However, the flow system preferably simulates certain physiological conditions to provide mechanical and/or biological features of interest. In some circumstances, it is desirable to maintain and/or introduce viable cells that require suitable conditions to maintain their normal function.
Various medical devices have been designed particularly for contact with a patient's body fluids and/or tissues. This contact can be sufficiently long such that surface interactions between the medical device and the patient's fluids and/or tissues become significant. For example, the host interaction with the medical device can lead to degradation, such as calcification of the medical device. Relevant medical devices include, for example, catheters and, especially, prostheses.
Catheters include percutaneous devices that penetrate the skin to provide access to a body system. Prostheses, i.e., prosthetic devices, are used to repair or replace damaged or diseased organs, tissues and other structures in humans and animals. Implantable prostheses, such as heart valve prostheses, are generally biocompatible since they are typically implanted for extended periods of time.
Prostheses can be constructed from natural materials, such as tissue, synthetic materials or a combination thereof. Prostheses formed from purely synthetic materials, such as mechanical heart valve prostheses, can be manufactured, for example, from biocompatible metals, ceramics, carbon materials, such as graphite, polymers, such as polyester, and combinations thereof.
Mechanical heart valves can be manufactured with rigid occluders or leaflets that pivot to open and close the valve. Although mechanical heart valves with rigid pivoting occluders have the advantage of proven durability through decades of use, they are associated with blood clotting on or around the prosthetic valve. For this reason, patients with implanted mechanical heart valves remain on anticoagulants for as long as the valve remains implanted.
Heart valve prostheses can be constructed with flexible tissue leaflets or polymer leaflets. Prosthetic tissue heart valves can be derived from, for example, porcine heart valves or manufactured from other biological materials, such as bovine pericardium. Prosthetic heart valves made from biological materials generally have profile and surface characteristics that provide laminar blood flow. Therefore, intravascular clotting may be less likely to occur than with mechanical heart valves.
However, some prosthetic tissue heart valves are limited by a tendency to fail beginning about seven years following implantation. Calcification, i.e., the deposition of calcium salts, especially calcium phosphate (hydroxyapatite), appears to be a major cause of degeneration. Thus, tissue heart valves are generally used for older patients who experience less calcification and require the valve for shorter lengths of time. In addition, various approaches have been developed to reduce the effects of calcification, such that tissue heart valves will have greater durability. As these approaches achieve demonstrated long term effectiveness, tissue heart valves will find greater use.
A disadvantage of currently available tissue and polymer based prostheses is their inability to remodel. Long term durability may be affected by the lack of viable cells to populate the implanted substrate, to inhibit calcification and other forms of degeneration and to carry out maintenance functions. In addition, the presence of viable cells may result in improved hemodynamic performance and/or reduced thrombogenicity.
Prostheses generally are manufactured to last for significant periods of time with very high reliability. Therefore, in the development of prostheses, the prostheses may be subjected to suitable conditions to simulate in vivo function. Similarly, approximate physiological conditions may be significant for testing and/or preparation of prostheses since the prostheses may include viable cells or serve as an attachment and/or growth substrate for viable cells removed from their surroundings. Since natural biological conditions can be useful for the testing of certain prostheses and the preparation of other prostheses, it is desirable to have appropriate apparatuses to simulate natural biological conditions.